Several genetic and acquired pathologic conditions of the musculoskeletal system, such as, arthritis, damage to ligament, cartilage, and meniscus may be amenable to gene therapy. Event through ex vivo gene transfer using synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited due mainly to a transient transgene expression. Although the cause of this transient expression is unknown, the use of a cell that becomes post-mitotic with differentiation such as myoblasts may allow high level of gene transfer and persistent transgene expression. In fact, we have observed that myoblasts can be transduced with a higher efficiency than synovial cells using the same adenoviral solution in vitro. In addition we have observed that engineered myoblasts are capable of adhering as well as differentiating into post-mitotic myotubes and myofibers into several structures in the joint including the ligament, meniscus, and synovium. The presence of post-mitotic myofibers in the knee joint opens up the possibility for long term expression of the secreted protein. Here we present a series of experiments aimed at validating the hypothesis that autologuous myoblast transfer using retrovirally-transduced primary myoblasts may achieve a high level of gene transfer and a persistent transgene expression into the joint. We then plan to investigate whether myoblast can deliver a persistently high level of IL1-Ra production into an arthritic knee to eventually alleviate the symptoms of arthritis.